Methods of reducing non-specific interaction in metal nanoparticle assays

The present invention discloses methods of reducing non-specific interactions of interfering species present in a sample in metallic nanoparticle-based assays, thereby increasing the sensitivity of these assays. In particular, the methods entail neutralizing the chemical reactivity of functional groups present in interfering species by addition of a neutralizing agent, such as an alkylating agent or heavy metal ion. The methods are especially useful in assays for the detection of analytes in biological samples. Reagent kits and assay mixtures for the practice of the described methods are also disclosed.